Means and method for diagnosis and treatment of alzheimer's disease

Abstract

The disclosure provides an extracellular target for Alzheimer's disease selected from the tetraspanin web family. The disclosure also provides diagnostic methods for the use as a target for detection of Alzheimer's disease in a subject. In addition, screening methods are provided for selecting compounds that bind or down-regulate the expression of the target.

1 . A method of detecting or diagnosing the presence of Alzheimer's disease or a predisposition to Alzheimer's disease in a subject, the method comprising:
 determining the expression level of TSPAN6 in a biological sample derived from the subject, wherein an increase of said level compared to a normal control of said gene indicates that the subject suffers from or is at risk of developing Alzheimer's disease,   wherein the expression level is determined by any one method selected from the group consisting of: a) detecting a mRNA of TSPAN6, b) detecting a protein encoded by TSPAN6 and c) detecting the biological activity of the protein encoded by TSPAN6.   
     
     
         2 . A method according to  claim 1  wherein an increase of the level of TSPAN6 is correlated with the disease stage of Alzheimer's disease. 
     
     
         3 . The method according to  claim 1 , wherein said increase is at least 10% greater than said normal control. 
     
     
         4 . The method according to  claim 1 , wherein said biological sample is serum, plasma, saliva, CSF or urine. 
     
     
         5 . A kit for detecting or diagnosing Alzheimer's disease in a subject, the kit comprising:
 a detection agent that binds to a transcription or translation product of TSPAN6.   
     
     
         6 . A method of treating or preventing Alzheimer's disease in a subject, the method comprising:
 administering to the subject a compound that inhibits the biological activity of TSPAN6, the compound selected from the group consisting of a short interference RNA for TSPAN6, an antibody against TSPAN6 or a gene product thereof, and a peptide or an extracellular fragment derived from TSPAN6 so as to treat or prevent Alzheimer's disease in the subject.   
     
     
         7 . A pharmaceutical composition comprising an effective amount of an isolated siRNA comprising a sense RNA strand and an antisense RNA strand, wherein the sense and the antisense RNA strands form an RNA duplex, and wherein the sense RNA strand comprises a nucleotide sequence identical to a target sequence of about 19 to about 25 contiguous nucleotides in SEQ ID NO:1. 
     
     
         8 . A pharmaceutical composition comprising an effective amount of an antibody that specifically binds to SEQ ID NO:2. 
     
     
         9 . A method of screening for a candidate compound for treating or preventing Alzheimer's disease, said method comprising the steps of:
 a) contacting a test compound with a polypeptide encoded by TSPAN6,   b) detecting binding activity between the polypeptide and the test compound or detecting biological activity of the polypeptide of step a), and   c) selecting a compound that binds to the polypeptide or selecting a compound that suppresses biological activity of the polypeptide in comparison with the biological activity in the absence of the test compound.   
     
     
         10 . A method of screening for a candidate compound for treating or preventing Alzheimer's disease, said method comprising the steps of:
 a) contacting a test compound with a cell expressing TSPAN6, and   b) selecting a compound that reduces the expression level of TSPAN6.   
     
     
         11 . A method of screening for a candidate compound for treating or preventing Alzheimer's disease, said method comprising:
 contacting a test compound with a cell into which a vector comprising a transcriptional regulatory region of TSPAN6 gene and a reporter gene that is expressed under control of said transcriptional regulatory region has been introduced,   measuring expression or activity of said reporter gene, and   selecting a compound that reduces the expression or activity level of said reporter gene, as compared to a level in the absence of the test compound.   
     
     
         12 . The method according to  claim 2 , wherein the increase is at least 10% greater than the normal control. 
     
     
         13 . The method according to  claim 2 , wherein the biological sample is serum, plasma, saliva, cerebrospinal fluid, or urine. 
     
     
         14 . The method according to  claim 3 , wherein the biological sample is serum, plasma, saliva, cerebrospinal fluid, or urine. 
     
     
         15 . The method according to  claim 12 , wherein the biological sample is serum, plasma, saliva, cerebrospinal fluid, or urine.